La gestione del paziente con FA: ruolo dei NAO
21-22 Novembre 2014
Fossano
NAO: real world
ed esperienza locale
Dott. Sergio Agosti
Cardiologo,
Ospedale Novi Ligure (AL)
www.docvadis.it/agostisergio
[email protected]
Dabigatran in numeri….
• 60000 pz nei trials
•2170 articoli - studi clinici (PUBMED)
•Almeno 260000 pz nei registri
(Minisentinel, Medicare, registro AHA)
•50000 pz in GLORIA
•Oltre 3 milioni di pz trattati nel mondo
2 aa
2,3 aa
RELY-ABLE®: Risultati di efficacia
5851 pazienti sono stati seguiti mediamente per 2,3 anni
D 150 mg BID
D110 mg BID
(%/yr)
(%/yr)
Ictus o SEE
1.46
Tutti i casi di ictus
Evento
HR
IC al 95%
1.60
0.91
0.69–1.20
1.24
1.38
0.89
0.66–1.21
ischemici
1.15
1.24
0.92
0.67–1.27
emorragici
0.13
0.14
0.89
0.34–2.30
Infarto del miocardio
0.69
0.72
0.96
0.63–1.45
Embolia polmonare
0.13
0.11
1.14
0.41–3.15
D150 e D110 = rispettivamente dabigatran 150 e 110 mg due volte al giorno; HR = hazard ratio
SEE = systemic embolic event = evento embolico sistemico
Connolly SJ, et al. Randomized Comparison of the Effects of Two Doses of Dabigatran Etexilate on Clinical Outcomes Over 4.3 Years: Results of the RELY-ABLE Doubleblind Randomized Trial. CS.04. Clinical Science: Special Reports: Valvular Heart Disease, PAD, Atrial Fibrillation: International Perspectives.  Presented on 7
November 2012 at the American Heart Association Scientific Sessions 2012.
RELY-ABLE®: risultati di sicurezza
5851 pazienti sono stati seguiti mediamente per 2,3 anni
Solo RELY-ABLE®
Evento
Sanguinamento maggiore
D150 mg BID D110 mg BID
(%/yr)
(%/yr)
HR
IC al 95%
3.74
2.99
1.26
1.04–1.53
pericolo di vita
1.79
1.57
1.14
0.87–1.49
GI
1.54
1.56
0.99
0.75–1.31
Intra-cranico
0.33
0.25
1.31
0.68–2.51
Extra-cranico
3.43
2.82
1.23
1.01–1.49
Fatale
0.24
0.25
0.94
0.46–1.89
9.70
8.19
1.21
1.07–1.36
Sanguinamento minore
D150 e D110 = rispettivamente dabigatran 150 e 110 mg due volte al dì; HR = hazard ratio
Connolly SJ, et al. Randomized Comparison of the Effects of Two Doses of Dabigatran Etexilate on Clinical Outcomes Over 4.3 Years: Results of the RELY-ABLE Doubleblind Randomized Trial. CS.04. Clinical Science: Special Reports: Valvular Heart Disease, PAD, Atrial Fibrillation: International Perspectives.  Presented on 7
November 2012 at the American Heart Association Scientific Sessions 2012.
Medicare analysis: results
Incidence rate per 1000 personyears
Adjusted HR
(95% CI)
Dabigatran
Warfarin
Ischaemic stroke
11.3
13.9
0.80 (0.67-0.96)
Intracranial haemorrhage
3.3
9.6
0.34 (0.26-0.46)
Major gastrointestinal
bleeding
34.2
26.5
1.28 (1.14-1.44)
Acute myocardial infarction
15.7
16.9
0.92 (0.78-1.08)
Mortality
32.6
37.8
0.86 (0.77-0.96)
Dabigatran was associated with a lower risk of ischaemic stroke, intracranial
haemorrhage and death than warfarin.
Risk of MI was similar for dabigatran and warfarin.
Primary findings for dabigatran are based on analysis of both 75 mg and 150 mg
together without stratification by dose. Warfarin is the reference group. CI = confidence
interval; HR = hazard ratio; MI = myocardial infarction;
Available at: www.fda.gov/Drugs/DrugSafety/ucm396470.htm (accessed May 2014)
Medicare analysis: results
Incidence rate per 1000 personyears
Adjusted HR
(95% CI)
Dabigatran
Warfarin
Ischaemic stroke
11.3
13.9
0.80 (0.67-0.96)
Intracranial haemorrhage
3.3
9.6
0.34 (0.26-0.46)
Major gastrointestinal
bleeding
34.2
26.5
1.28 (1.14-1.44)
Acute myocardial infarction
15.7
16.9
0.92 (0.78-1.08)
Mortality
32.6
37.8
0.86 (0.77-0.96)
Dabigatran was associated with a lower risk of ischaemic stroke, intracranial
haemorrhage and death than warfarin.
Risk of MI was similar for dabigatran and warfarin.
Primary findings for dabigatran are based on analysis of both 75 mg and 150 mg
together without stratification by dose. Warfarin is the reference group. CI = confidence
interval; HR = hazard ratio; MI = myocardial infarction;
Available at: www.fda.gov/Drugs/DrugSafety/ucm396470.htm (accessed May 2014)
Medicare analysis: results
Incidence rate per 1000 personyears
Adjusted HR
(95% CI)
Dabigatran
Warfarin
Ischaemic stroke
11.3
13.9
0.80 (0.67-0.96)
Intracranial haemorrhage
3.3
9.6
0.34 (0.26-0.46)
Major gastrointestinal
bleeding
34.2
26.5
1.28 (1.14-1.44)
Acute myocardial infarction
15.7
16.9
0.92 (0.78-1.08)
Mortality
32.6
37.8
0.86 (0.77-0.96)
Dabigatran was associated with a lower risk of ischaemic stroke, intracranial
haemorrhage and death than warfarin.
Risk of MI was similar for dabigatran and warfarin.
Primary findings for dabigatran are based on analysis of both 75 mg and 150 mg
together without stratification by dose. Warfarin is the reference group. CI = confidence
interval; HR = hazard ratio; MI = myocardial infarction;
Available at: www.fda.gov/Drugs/DrugSafety/ucm396470.htm (accessed May 2014)
Medicare analysis: results
Incidence rate per 1000 personyears
Adjusted HR
(95% CI)
Dabigatran
Warfarin
Ischaemic stroke
11.3
13.9
0.80 (0.67-0.96)
Intracranial haemorrhage
3.3
9.6
0.34 (0.26-0.46)
Major gastrointestinal
bleeding
34.2
26.5
1.28 (1.14-1.44)
Acute myocardial infarction
15.7
16.9
0.92 (0.78-1.08)
Mortality
32.6
37.8
0.86 (0.77-0.96)
Dabigatran was associated with a lower risk of ischaemic stroke, intracranial
haemorrhage and death than warfarin.
Risk of MI was similar for dabigatran and warfarin.
Primary findings for dabigatran are based on analysis of both 75 mg and 150 mg
together without stratification by dose. Warfarin is the reference group. CI = confidence
interval; HR = hazard ratio; MI = myocardial infarction;
Available at: www.fda.gov/Drugs/DrugSafety/ucm396470.htm (accessed May 2014)
Global Registry on Long-Term Oral
Antithrombotic Treatment in AF Patients
• Collection of data on dabigatran in countries/regions and globally
• Increase knowledge on AF patients, treatment patterns, and outcome events
in a real-world setting
• Involvement of up to 2200 physicians worldwide: GPs, cardiologists,
neurologists, internists, geriatricians, etc – hospital based or private practice
up to
56 000
patients
2200
sites
up to
50 countries
Piani terapeutici AIFA compilati al 12 luglio 2014
72000 Pradaxa®
Numero PT
46000 Xarelto®
17000 Eliquis®
http://www.agenziafarmaco.gov.it/sites/default/files/EurDURG_28082014_Xoxi.pdf
Analisi NAO Regione Piemonte
2013
ASL RES
2014 (gennaio - agosto)
Warfarin
B01AA03
Warfarin
B01AA03
di cui Soggetti che
Soggetti Warfarin
Soggetti che
consumano
nel 2013 e che nel
hanno iniziato a
entrambi
2014 sono passati
consumare solo
(Warfarin e NAO)
ai NAO
NAO nel 2014
nel 2014
Soggetti che
hanno assunto
Warfarin 2013 x Warfarin 2014 x
almeno una volta i 1.000 abitanti
1.000 abitanti
NAO nel 2014
NAO 2014 x
1.000 abitanti
201
9.202
7.955
442
204
717
1.159
19,2
16,6
2,4
202
8.654
7.605
251
121
376
627
20,5
18,0
1,5
203
11.412
9.984
566
260
723
1.289
19,4
17,0
2,2
204
9.986
8.628
401
194
469
870
19,2
16,6
1,7
205
5.525
4.907
205
114
358
563
17,8
15,8
1,8
206
2.294
1.871
176
89
288
464
13,1
10,7
2,7
207
2.996
2.592
108
53
168
276
17,2
14,9
1,6
208
4.910
4.140
268
162
379
647
14,0
11,8
1,8
209
1.917
1.609
68
29
155
223
11,1
9,4
1,3
210
7.518
6.454
413
145
573
986
17,9
15,3
2,3
211
2.700
2.136
382
135
367
749
15,7
12,4
4,4
212
3.363
2.874
164
67
291
455
16,2
13,8
2,2
213
7.333
6.070
522
197
753
1.275
16,4
13,6
2,9
Totale
77.810
66.825
3.966
1.770
5.617
9.583
17,5
15,1
2,2
COSTO-EFFICACIA DABIGATRAN
Mennini F. et al., Farmeconomia e percorsi 2011; 12(1): 63-69
ESPERIENZA DELL’OSPEDALE
DI NOVI LIGURE
NAO
TOTALE 392 pz
ESPERIENZA DELL’OSPEDALE
DI NOVI LIGURE
DABIGATRAN
•252 pazienti in Dabigatran
•60% uomini - 40% donne
•Età media 77 anni (range 42-93)
•Primo paziente trattato il 1 luglio 2013
•79% Piemonte - 21% Liguria
•CHADSVASC medio 3.9 (range 1-8)
•HASBLED medio 2 (range 0-5)
ESPERIENZA DELL’OSPEDALE
DI NOVI LIGURE
•Scompenso cardiaco 27% (68 pt)
•Ipertensione arteriosa 88% (223 pt)
•Diabete 17% (43 pt)
•Pregresso ictus 18% (45 pt)
•Pregressa CAD 18% (44 pt)
•Pregresso sanguinamento significativo 7% (18 pt)
•Labile INR 20% (52 pt)
•Terapia concomitante 4% (11 pt)
•TAO experience 43% (108 pt) RELY 50%
•TTR medio 66% TTR medio RELY 64%, ROCKET 55%
CHADSVASC
MEDIO 3,9
CHADSVASC
Come abbiamo somministrato il
Dabigatran?
110 MG BID 69% (174 PZ)
Età media 80 anni (range 60-93)
Cl creat media 44 ml/min (range 33-77)
150 MG BID 31% (77 PZ)
Età media 70 anni (range 42-85)
Cl creat media 84 ml/min (range 58-109)
STADIO CHADSVASC CON LE DUE DOSI DI DABIGATRAN
% PAZIENTI
CHADSVASC
CONTINUAZIONE O SOSPENSIONE DAL
TRATTAMENTO
FOLLOW UP medio 8 mesi
Sospensione 5% (13 pazienti)
•Dispepsia 7% (17 pz)
•Sospensioni per dispepsia (2,5% - 7 pz)
•Ischemie cerebrali (0,8% - 2 pz)
•Emorragie maggiori (0,4% - 1 pz)
•Emorragie minori (3% - 8 pz)
•Emorragie cerebrali (0%)
•Orticaria (1,5% - 4 pz)
•CVE (3% - 8 pz) senza complicanze
Assume that NAOs have been on the market for 5 year
➢A new drug comes to the market. Compared to NAOs, the new drug has:
- cheaper
- antidote
- requirement for monthly monitoring to adjust dose
- many food and drug interactions
- 25% increased relative risk of stroke/systemic embolism
- nearly 50% increased relative risk of major bleeding
- approx. 2.5 times the rate of ICH
- 10% increased relative risk of mortality
➢Would Warfarin be approved by regulatory authorities now?
www.docvadis.it/agostisergio
3487760927
0143-332395